Drug Resistance Mechanism of Enterobacteriaceae and Its Strategies

Carbapenem-Resistant Enterobacteriaceae Infection Clinical Trial

Official title:

Evaluation of Ceftazidime-avibactam Plus Aztreonam in Patients Infected by MBL-producing Enterobacterales and CRISPR/Cas9-based Strategy for Curing Drug-resistant Genes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05850871
• Other study ID #: JNQH-CT-231001
• Status: Recruiting
• Phase: N/A
• Start date: January 6, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: April 2023
• Source: Qianfoshan Hospital
• Contact: Mingju Hao, Doctor
• Phone: 8613012995730
• Email: haomingju[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The first aim of this study is to explore the drug resistance mechanism of Enterobacteriaceae bacteria and to evaluate the treatment effect of ceftazidime-avibactam (CAZ-AVI) in combination with aztreonam (ATM) against Metallo-β-lactamases (MBL) producing Enterobacterales in vivo. The investigators then use CRISPR/Cas9 technology to remove Enterobacteriaceae bacteria resistance and virulence genes

Description:

Clinical information of subjects, including diseases, departments, medication history, days of hospitalization, and treatment outcomes will be collected; Bacterial species names will be identified and drugs sensitivity will be detected; For patients with bloodstream infection of MBL-producing Enterobacterales, ceftazidime-avibactam (CAZ-AVI) was administered at the dose of 2.5 g every 8 hours and aztreonam (ATM) at the dose of 2 g every 8 hours.

The primary outcome measure was 30-day all-cause mortality, while secondary outcomes were clinical failure at day 14 and length of stay (LOS) after bloodstream infection diagnosis. Cox regression analysis, including a propensity score (PS) for receiving CAZ-AVI plus ATM, was conducted to assess the primary and secondary outcomes. The CRISPR/Cas9 gene curation technology was used to eliminate the drug resistance and virulence factors of Enterobacteriaceae in the mouse intestinal colonization model.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 427
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Subjects clinically suspected of infection caused by Enterobacterales

• Subjects with bloodstream infection by MBL-producing Enterobacterales

Exclusion Criteria:

• Infections caused by viruses, fungi, atypical pathogens, and other non-Enterobacteriaceae bacteria

• subjects who are unwilling to enter the research group

Related Conditions & MeSH terms

• Carbapenem-Resistant Enterobacteriaceae Infection
• Enterobacteriaceae Infections

Intervention

Drug:
• CAZ/AVI plus Aztreonam
Samples of the patients will be examined such as the routine blood test, blood culture et al.

Other:
• Conventional treatment
Conventional treatment

Locations

Country	Name	City	State
China	Mingju Hao	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Qianfoshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales.	Evaluation of the efficienty of CRISPR/Cas9 technique to cure resistance genes in a mouse model colonized by multidrug resistant enterobacteriaceae. Curation index as assessed by MBL producing Enterobacterales compared with MBL negative Enterobacterales isolated from the feces sample.	two years
Primary	30-day all-cause mortality	The primary outcome measure was 30-day all-cause mortality	two years
Primary	clinical failure at day 14	severe comorbidities, mechanical ventilation or septic shock at day 14	two years
Primary	length of stay after diagnosis	length of stay (LOS) after blood stream infection diagnosis	two years
Secondary	Positive rate of Metallo-ß-lactamases (MBL) producing Enterobacterales	Positive rate and subtype distribution of Metallo-ß-lactamases (MBL) producing Enterobacterales	two years